An FDA panel rejected ridaforolimus as a maintenance therapy for patients with soft-tissue or bone sarcoma.
Merck seeks approval for the indication in patients who had undergone at least four cycles of chemotherapy with no sign of disease progression.
The FDA’s Oncologic Drugs Committee, however, opposed the request by a 13-1 vote, noting the drug’s benefits did not outweigh potentially serious side effects. The FDA often follows the advisory committee’s recommendations but is not obligated to do so.
The committee based its decision on ridaforolimus (Taltorvic), an inhibitor of mammalian target of rapamycin (mTOR), on results of one phase 3 trial and two phase 2 trials.
In the phase 3 trial, 711 patients with metastatic soft-tissue or bone sarcoma were randomly assigned to ridaforolimus or placebo. Follow-up continued until disease progression, withdrawal or death.
The patients assigned to ridaforolimus had a median PFS of 17.7 weeks, compared with 14.6 weeks for placebo (P=.0001). The difference in median OS (20.8 months for ridaforolimus vs. 19.6 months for placebo) was non-significant.
Rates of grade-3/4 adverse events, as well as discontinuation due to adverse events, were higher in the ridaforolimus group. The rates of three significant adverse events — pneumonitis (10% vs. 0.6%), renal failure (10% vs. 1%) and hypersensitivity (10% vs. 2%) — were higher in those assigned to ridaforolimus than placebo. About 82% of patients assigned to ridaforolimus reported stomatitis, while 38% reported rash and 32% reported diarrhea.